Collagen, elastin and proteoglycans are the principal structural elements of the connective tissues. The type and quantity of collagen present in a tissue seems to be responsible for its functional properties. Since environmental factors (nutrients, O2, hormones, lysosomal enzymes, etc.) affect cell function, we plan to investigate how they alter the cells ability to synthesize collagen, in particular how it affects the nature of the molecules synthesized. FOR THIS PURPOSE: 1. We shall evaluate the types of collagen (I, II, III and IV) produced in vivo in organ and cell culture. We shall be working with fibroblasts from various origins, chondrocytes, embryonic muscle cells, endothelial cells, and smooth muscle cells. 2. The behavior of these cells in the organ environment shall be compared to that of cells in culture, at various passages following release from the tissue. 3. How does the pre-existing matrix protect cells from the environment? We know that cells in culture "derepress" quite readily and allow the expression of genes masked in the normal tissue environment. 4. We hope that answering these questions will allow us to understand some of the pathologies of the connective tissue as well as learning something about their genetic control of specific protein synthesis (in our case collagen). With this information we should be capable of further understanding some genetic and degenerative diseases and hopefully modifying cell function to restore their biosynthetic pattern to normal. BIBLIOGRAPHIC REFERENCES: Ananthanarayanan, S. and Nimni, M.E. Collagen of Rat Skin and Bovine Articular Cartilage: Their Hydrodynamic Properties During Interactions with Proteoglycans. Extracellular Matrix Influences on Gene Expression. Eds. Slavkin and Greulich, Academic Press, 1975, p. 311-320. Nimni, M. E. Molecular Structure and Function of Collagen in Normal and Diseased Tissues. Dynamics of Connective Tissue Macromolecules. Eds. Burleigh and Poole. North-Holland Publishing Company, 1975, p. 51 to 79.